This project will explore the following new approaches to tumor immunotherapy: (1) Amplification of tumor immunity by removing normal or pathological regulatory restraints on the immune mechanism. This will include studies of the levels of immune-inhibitory factors in the serum of tumor patients, attempts to demonstrate and characterize inhibitory factors produced or induced by tumors, development of a radio-immunoassay for a serum inhibitory factor associated with alpha-globulins, and attempts to antagonize or remove inhibitors from tumor-bearing animals. A related study will explore the therapeutic effects of an anti-mitotic agent produced by lymphocytes in response to immune stimulation. (2) Immunotherapy with diphtheria toxin conjugated to tumor-specific antibodies. This will include attempts to prepare immunoadsorbents from purified, solubilized tumor-specific antigens in order to improve the purity of antibody-toxin conjugates, studies of the chemistry of tumor-specific antigens, and correlation of antigenic with biochemical changes on the surface of tumor cells, with emphasis on deficiencies in the synthesis of cell-surface polysaccharides. (3) Antitumor therapy with irradiation, bone marrow transplantation, and antitumor viruses. This will include an investigation of the antileukemic potential of lymphocytic choriomeningitis virus and its variants in irradiated mice, and a study of the interaction between this virus, host immunity, and the expression of leukemia-associated antigens on leukemic cell surfaces. (4) Amplification of tumor immunity with RNA from immunized donors. This will include studies of the optimal methods for preparing tumor-immune RNA, optimal treatment schedules, and the maximum immunity achievable with this form of therapy.